cholesteryloxyacetic acid | 30656-77-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: cholesteryloxyacetic acid
• 英文别名: cholest-5-en-3β-yloxyacetic acid；Cholest-5-en-3beta-yloxyacetic acid；2-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]acetic acid
• CAS: 30656-77-0
• 化学式: C₂₉H₄₈O₃
• 分子量: 444.698
• InChiKey: VHSCWUOENVSGKM-OHPSOFBHSA-N

物化性质

• 沸点：
  558.0±33.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cholesteryloxyacetic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氯乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 [(2R,3S,5R)-3-[2-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]acetyl]oxy-5-[5-methyl-2,4-dioxo-3-(pyridin-4-ylmethyl)pyrimidin-1-yl]oxolan-2-yl]methyl 2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]acetate
  参考文献：
  名称：

  Cholesterol-Based Nucleolipid-Ruthenium Complex Stabilized by Lipid Aggregates for Antineoplastic Therapy

  摘要：

  A novel ruthenium complex, linked to a cholesterol-containing nucleolipid (named ToThyCholRu), stabilized by lipid aggregates for antineoplastic therapy is presented. In order to retard the degradation kinetics typically observed for several ruthenium-based antineoplastic agents, ToThyCholRu is incorporated into a liposome bilayer formed by POPC. The resulting nanoaggregates contain up to 15% in moles of the ruthenium complex, and are shown to be stable for several weeks. The liposomes host the ruthenium nucleolipid complex with the metal ion surrounded by POPC lipid headgroups and the steroid moiety inserted in the more external acyl chain region. These ruthenium-containing liposomes are more effective in inhibiting the growth of cancer cells than a model NAMI-A-like ruthenium complex, prepared for a direct evaluation of their anti-proliferative activity. These results introduce new perspectives in the design of innovative transition-metal-based supra-molecular systems for anticancer drug vectorization.

  DOI：

  10.1021/bc200565v
• 作为产物：
  描述：

  胆固醇 在 三氟化硼乙醚 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 cholesteryloxyacetic acid
  参考文献：
  名称：

  Design of potent Mincle signalling agonists based on an alkyl β-glucoside template

  摘要：

  将天然免疫受体Mincle的强效信号激动剂开发出来，可以轻松地从辛基和月桂基β-D-葡萄糖苷表面活性剂中制备。

  DOI：

  10.1039/d0cc00670j
• 作为试剂：
  描述：

  tert-butyl cholest-5-en-3β-yloxyacetate 、 乙醚 在 cholesteryloxyacetic acid 作用下， 反应 5.0h， 以to afford Cholest-5-en-3β-yloxyacetic acid (general formula IX, where n2=1; 99 mg, 100%)的产率得到cholesteryloxyacetic acid
  参考文献：
  名称：

  Lipopolyamines of spermine type for construction of liposomal transfection systems

  摘要：

  本发明提供了一种新型的精胺类脂质胺化合物，其通式为I，其中X为C-N键或氨基聚乙二醇羧酰胺连接基或o-羟基烷基羧酰胺连接基或ω-羟基烷基羧酰胺聚乙二醇羧酰胺连接基，而疏水域Y为在C（2）位置对称分支的酰基或胆固醇。本发明还提供了制备所述脂质胺化合物的方法以及它们用于构建多阳离子脂质体药物载体的用途。

  公开号：

  US09393200B2

文献信息

• Lipids, lipid compositions, and methods of using them
  申请人：Baryza Jeremy

  公开号：US09301923B2

  公开（公告）日：2016-04-05

  Disclosed are formulation and optimization protocols for delivery of therapeutically effective amounts of biologically active agents to liver, tumors, and/or other cells or tissues. Also provided are compositions and uses for cationic lipid compounds of formula (I). The invention also relates to compositions and uses for stealth lipids of formula (XI). Also provided are processes for making such compounds, compositions, and formulations, plus methods and uses of such compounds, compositions, and formulations to deliver biologically active agents to cells and/or tissues.

  揭示了用于将生物活性剂量有效传递至肝脏、肿瘤和/或其他细胞或组织的配方和优化协议。还提供了具有式(I)的阳离子脂质化合物的组成物和用途。该发明还涉及具有式(XI)的隐身脂质的组成物和用途。此外，还提供了制备这类化合物、组成物和配方的方法，以及利用这类化合物、组成物和配方将生物活性剂传递至细胞和/或组织的方法和用途。
• Sterol-modified PEG lipids: alteration of the bilayer anchoring moiety has an unexpected effect on liposome circulation
  作者：Aaron Dolor、Paul Kierstead、Zhipeng Dai、Francis C. Szoka

  DOI：10.1039/c8cc05011b

  日期：——

  We synthesized and characterized two novel sterol-anchored polyethylene glycols (PEG) as potential alternatives to conventional phosphatidylethanolamine-PEGs.

  我们合成并表征了两种新型的固醇锚定聚乙二醇（PEG），作为传统磷脂酰乙醇胺-PEG的潜在替代品。
• LIPOPOLYAMINES OF SPERMINE TYPE FOR CONSTRUCTION OF LIPOSOMAL TRANSFECTION SYSTEMS
  申请人：USTAV ORGANICKE CHEMIE A BIOCHEMIE AV CR, V.V.I.

  公开号：US20150018436A1

  公开（公告）日：2015-01-15

  The invention provides new lipopolyamines of spermine type of the general formula I, wherein X is C—N bond or aminopolyethyleneglycolcarboxamide linker or o-hydroxy-alkylcarboxamide linker or ω-hydroxyalkylcarboxamidopolyethyleneglycol-carboxamide linker, and wherein a hydrophobic domain Y is an acyl symmetrically branched in the position C(2) or cholesteryl. The invention further provides a method of preparation of said lipopolyamines and their use for construction of polycationic liposomal drug carriers.

  该发明提供了一种新的通式I的脂质聚胺，其中X是C—N键或氨基聚乙二醇羧酰胺连接物或o-羟基烷基羧酰胺连接物或ω-羟基烷基羧酰胺聚乙二醇羧酰胺连接物，其中疏水域Y是在位置C(2)处对称分支的酰基或胆固醇。该发明还提供了所述脂质聚胺的制备方法及其用于构建多阳离子脂质体药物载体的用途。
• Liposomal sustained-release delivery systems for intravenous injection. I. Physicochemical and biological properties of newly synthesized lipophilic derivatives of mitomycin C.
  作者：YUJI TOKUNAGA、TOMOAKI IWASA、JIRO FUJISAKI、SEIJI SAWAI、AKIRA KAGAYAMA

  DOI：10.1248/cpb.36.3060

  日期：——

  1a-N-Stearoyl mitomycin C (MMC) and six 1a-N-substituted derivatives of MMC possessing the cholesteryl moiety with different spacers were synthesized, and their biopharmaceutical properties were studied to assess the feasibility of such derivatives as prodrugs for intravenously injectable liposomal sustained-release carrier systems. All compounds showed increased lipophilic indices (logk'0) in high performance liquid chromatography. It was found that all the derivatives could be almost completely entrapped in liposomes, although MMC itself was hardly encapsulated. The derivatives with the exception of cholesteryloxycarbonyl MMC (II) and N-(cholesteryloxy-carbonyl)-4-aminophenylacetyl MMC (VI) were converted to the parent drug in rat serum. The suceptibility of the compounds to hydrolysis was strongly affected by the spacer structure between MMC and the cholesteryl moiety. Cholesteryloxyacetyl MMC (IV) was converted to MMC mainly by chemical hydrolysis. N-(Cholesteryloxycarbonyl)glycyl MMC (III) was also hydrolyzed to MMC chemically but in this case hydrolysis was accelerated in the presence of mouse, rat and human serum. No species differences were observed in these bioactivation phenomena. Entrapment of derivatives III and IV in liposomes resulted in enhancement of the stability against both chemical and enzymatic hydrolysis. The derivatives possessing the cholesteryl moiety were firmly associated with liposomes in the circulation, while stearoyl MMC (VIII) was rapidly recoved. These results suggest that derivatives III and IV have the potential to be utilized as lipophilic prodrugs for liposomal sustained-release carrier systems to be delivered by intravenous injection.

  1a-N-硬脂酰基丝裂霉素C（MMC）及其六种具有胆固醇基团的MMC衍生替代品（含不同的间隔基）被合成，并研究了它们的药物特性，以评估这些衍生物作为静脉注射脂质体长效释放载体系统的药物前体的可行性。所有化合物在高效液相色谱中显示出增加的脂溶性指数（logk'0）。发现所有衍生物几乎可以完全被包裹在脂质体中，尽管MMC本身很难被包裹。除了胆固醇氧甲酰MMC（II）和N-（胆固醇氧甲酰基）-4-氨基苯乙酰基MMC（VI）之外，所有其他衍生物在鼠血清中转化为其母体药物。这些化合物对水解作用的影响受到了MMC和胆固醇基团之间间隔基结构的强烈影响。胆固醇氧乙酰基MMC（IV）主要由化学水解转化为MMC。N-（胆固醇氧甲酰基）甘氨酰MMC（III）也被化学水解为MMC，但在这种情况下，在小鼠、大鼠和人类血清中的水解作用被加速。在这些生物活化现象中没有观察到物种差异。将III和IV衍生物包裹在脂质体中，增强了其抵御化学和酶水解的稳定性。具有胆固醇基团的衍生物在循环中与脂质体紧密结合，而硬脂酰MMC（VIII）则迅速恢复。这些结果表明，III和IV衍生物有可能作为脂质体长效释放载体系统的脂溶性药物前体，通过静脉注射进行输送。
• LIPIDS, LIPID COMPOSITIONS, AND METHODS OF USING THEM
  申请人：BARYZA Jeremy

  公开号：US20110200582A1

  公开（公告）日：2011-08-18

  Disclosed are formulation and optimization protocols for delivery of therapeutically effective amounts of biologically active agents to liver, tumors, and/or other cells or tissues. Also provided are compositions and uses for cationic lipid compounds of formula (I). The invention also relates to compositions and uses for stealth lipids of formula (XI). Also provided are processes for making such compounds, compositions, and formulations, plus methods and uses of such compounds, compositions, and formulations to deliver biologically active agents to cells and/or tissues.

  本文披露了用于将生物活性剂量有效传递至肝脏、肿瘤和/或其他细胞或组织的配方和优化方案。还提供了具有化学式（I）的阳离子脂质化合物的组成和用途。该发明还涉及具有化学式（XI）的隐身脂质的组成和用途。还提供了制备这种化合物、组成物和配方的方法，以及利用这些化合物、组成物和配方将生物活性剂传递至细胞和/或组织的方法和用途。